Retrovirus is a generic term of viruses belonging to Retroviridae, which have RNA as genome, and synthesize, in the primary step of self-replication, DNA using RNA as a template by the action of reverse transcriptase (RNA dependent DNA polymerase) they have. Retroviridae consists of three subfamilies (Oncovirinae, Lentivirinae, Spumavirinae). Retrovirus is known to infect and proliferate in various animals such as birds and mammals as hosts, and cause sarcoma, leukemia, cancer and the like. As retrovirus using human as a host, human T cell leukemia virus (HTLV), human immunodeficiency virus (HIV) and the like have been reported. HIV is known as a causative virus of acquired immunodeficiency syndrome (AIDS), a severe immunodeficiency.
AIDS has been suppressed to some extent by the development of compounds that inhibit reverse transcriptase and protease essential for HIV replication, and establishment of a combination therapy using such compounds. On the other hand, the emergence of resistant viruses is recognized as a major concern, and the development of a compound that inhibits a mechanism essential for HIV replication, which is other than reverse transcriptase and protease, has been desired.
HIV infects using, as a receptor, CD4 molecule presented on cellular membranes of helper T cell and macrophage. In this case, it requires an co-factor (coreceptor) that cooperates with CD4 molecule and promotes entry of the virus. As the coreceptor, chemokine (inflammatory cytokine) receptors CXCR4 and CCR5 have been identified at present (non-patent document 1).
As mentioned above, HIV recognizes CD4 and a series of chemokine receptors (e.g., CXCR4 and the like) of the target cell and enters the cell by fusion of viral envelope and cellular membrane. Therefore, a change in lipid, which is the constituent component of the membrane, is considered to affect HIV infection. Fenretinide (4-Hydroxyphenylretinoid), a retinoid analog, is known to specifically increase the ceramide level in the lipid component of membrane, and has already been reported to suppress intracellular entry of HIV (non-patent document 2, non-patent document 3). However, since fenretinide shows high cytotoxicity, its clinical application is difficult.    non-patent document 1: Berger, E. A., Doms, R. W., Fenyo, E.-M., Korber, B. T. M., Littman, D. R., Moore, J. P., Sattentau, Q. J., Schuitemaker, H., Sodroski, J., and Weiss, R. A. 1998. A new classification for HIV-1. Nature 391, 240.    non-patent document 2: Finnegan, C. M., Rawat, S. S., Puri, A., Wang, J. M., Ruscetti, F. W., and Blumenthal, R. 2004. Ceramide, a target for antiretroviral therapy. Proc. Natl. Acad. Sci. USA 101, 15452-15457.    non-patent document 3: Finnegan, C. M., and Blumenthal, R. 2006. Fenretinide inhibits HIV infection by promoting viral endocytosis. Antiviral Res. 69, 116-123.    non-patent document 4: Shidoji, Y., and Ogawa, H. 2004. Natural occurrence of cancer-preventive geranylgeranoic acid in medicinal herbs. J. Lipid Res. 45, 1092-1103.    non-patent document 5: Muto, Y., Moriwaki, H., and Saito, A. 1999. Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. N. Engl. J. Med. 340, 1046-1047.